Biomimetic approaches to tendon repair

Biomimetic approaches to tendon repair
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DOI:
10.1016/s1095-6433(02)00247-7
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发表时间:
2002-12-01
影响因子:
2.3
通讯作者:
Koob, TJ
Koob, TJ
中科院分区:
生物学3区
文献类型:
--
作者:
Koob, TJ

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肌腱中胶原纤维的线性组织导致拉伸载荷下低应变下的最佳刚度和强度。然而,这个组织使得修复断裂或撕裂的肌腱非常困难。目前连接钢筋束分裂端的锚固技术虽然提供了足够的机械强度以防止间隙,但不足以承载正常载荷。恢复肌腱一致性所需的固定方案导致修复部位瘢痕形成和限制偏移的外周粘连。这些问题进行审查,强调需要新的方法来修复肌腱,其中之一是仿生肌腱的发展。本文所述的实验性工作的目的是生产具有适当机械性能的生物相容性肌腱替代物,以便在手术修复后立即活动。去甲二氢愈创木酸(NDGA),一种来自杂酚油灌木的二儿茶酚,引起了重组胶原蛋白纤维的材料特性的剂量依赖性增加,与未处理的纤维相比,强度和刚度增加了100倍。优化NDGA处理的纤维的最大拉伸强度平均为90 MPa;这些纤维的弹性模量平均为580 MPa。这些属性是独立的应变速率范围从0.60至600毫米/分钟。疲劳试验确定,无论是强度还是刚度80 K周期后,在5%的应变受到影响。经处理的纤维对肌腱成纤维细胞无细胞毒性。成纤维细胞在NDGA处理过的胶原上正常贴壁增殖。NDGA纤维没有引起异物反应,也没有刺激体内六周的免疫反应。纤维存活6周,几乎没有断裂或降解的迹象。这里描述的聚合方案产生具有接近弹性固体的机械性能的纤维增强NDGA聚合物。NDGA处理纤维的强度、刚度和疲劳性能与肌腱相当。这些纤维与肌腱成纤维细胞具有生物相容性,并且在体内几乎不引起排斥反应或抗原反应。这些结果表明,NDGA聚合可以提供一种可行的方法,用于生产胶原材料,可用于桥接断裂或撕裂肌腱的间隙。NDGA纤维的肌腱样性质将允许手术修复后的早期活动。我们预测,这种新型生物材料加入的分离肌腱的及时加载将增强由定植成纤维细胞机械驱动的新肌腱的产生,并导致上级修复和快速恢复正常性能。(C)2002年爱思唯尔科技有限公司All rights reserved.
The linear organization of collagen fibers in tendons results in optimal stiffness and strength at low strains under tensile load. However, this organization makes repairing ruptured or lacerated tendons extremely difficult. Current suturing techniques to join split ends of tendons, while providing sufficient mechanical strength to prevent gapping, are inadequate to carry normal loads. Immobilization protocols necessary to restore tendon congruity result in scar formation at the repair site and peripheral adhesions that limit excursion. These problems are reviewed to emphasize the need for novel approaches to tendon repair, one of which is the development of biontimetic tendons. The objective of the empirical work described here was to produce biologically-based, biocompatible tendon replacements with appropriate mechanical properties to enable immediate mobilization following surgical repair., Nor-dihydroguaiaretic acid (NDGA), a di-catechol from creosote bush, caused a dose dependent increase in the material properties of reconstituted collagen fibers, achieving a 100-fold increase in strength and stiffness over untreated fibers. The maximum tensile strength of the optimized NDGA treated fibers averaged 90 MPa; the elastic modulus of these fibers averaged 580 MPa. These properties were independent of strain rates ranging from 0.60 to 600 mm/min. Fatigue tests established that neither strength nor stiffness were affected after 80 k cycles at 5% strain. Treated fibers were not cytotoxic to tendon fibroblasts. Fibroblasts attached and proliferated on NDGA treated collagen normally. NDGA fibers did not elicit a foreign body response nor did they stimulate an immune reaction during six weeks in vivo. The fibers survived 6 weeks with little evidence of fragmentation or degradation. The polymerization scheme described here produces a fiber-reinforced NDGA polymer with mechanical properties approaching an elastic solid. The strength, stiffness and fatigue properties of the NDGA treated fibers are comparable to those of tendon. These fibers are biocompatible with tendon fibroblasts and elicit little rejection or antigenic response in vivo. These results indicate that NDGA polymerization may provide a viable approach for producing collagenous materials that can be used to bridge gaps in ruptured or lacerated tendons. The tendon-like properties of the NDGA fiber would allow early mobilization after surgical repair. We predict that timely loading of parted tendons joined by this novel biomaterial will enhance mechanically driven production of neotendon by the colonizing fibroblasts and result in superior repair and rapid return to normal properties. (C) 2002 Elsevier Science Inc. All rights reserved.